Conventionally, in the development of pharmaceuticals, the determination of binding sites between constituent proteins of protein complexes is an important matter. For example, if the protein complex causing the pathological condition is known, a pharmaceutical candidate that inhibits the formation of the complex is designed based on the shape of a site (“binding site”) strongly related to the binding of constituent proteins.
In general, a protein complex is thought be formed by the binding of a constituent protein to another constituent protein by a weak noncovalent interaction at work between constituent proteins in close proximity. A binding site is a constituent protein site related to such an interaction. Therefore, geometric compliments (interlocking shapes) on molecular surfaces of adjacent constituent proteins, electrostatic compliments (positive and negative electrostatic potential occurring between adjacent surfaces), and the like are often searched for as clues.
A 3-D viewer that displays a 3-dimensional configuration of protein on the display of a computing device is known as technology that helps determine binding sites. Based on 3-dimensional structural data (typically, a file storing the types of atoms forming a protein and respective positions on a 3-dimensional coordinate system) of protein and obtained through structural analysis by X-ray, the 3-D viewer creates a figure depicting the 3-dimensional configuration of a protein as viewed from a given direction and displays the figure on the display of the computing device.
Various types of models for expressing the 3-dimensional configuration of a protein are known. For example, there is a model that expresses the shape of protein by the molecular surface obtained from 3-dimensional structural data and expresses the electrostatic potential at points on the molecular surface, by color (e.g., expresses positive electrostatic charge in blue and negative electrostatic charge in red).
Further, for an electrostatic-surface of a functional site (eF-site) that provides the shape and physical properties of a functional site of protein as a database, a tool called a PDBj Viewer that includes a function of displaying a 3-dimensional structure of protein by this type of model has been proposed (see, for example, Kinoshita, K., et al, “eF-site and PDBjViewer: database and viewer for protein functional sites”, Bioinformatics Vol. 20, No. 8, 2004, pp. 1329-1330). Technology has been disclosed that displays images using pixels as structural elements as well as technology that regards recessed surfaces of macromolecules such as proteins and nucleic acids as potential binding sites and uses the distance at which the binding sites and small molecule ligands can bind, to display ligand-binding pockets of the macromolecules (see for example, Japanese Laid-Open Patent Publication Nos. 2001-22936 and 2009-58499).
However, with the technologies above, if a complex of proteins is to be displayed 3-dimensionally, a problem arises in that adjacent molecular surfaces of proteins become hidden by surrounding molecular surfaces and cannot be seen.
FIG. 38 is diagram of a 3-dimensional model of a protein complex displayed on a display screen. In FIG. 38, an XY plane formed by an X axis and a Y axis, which is orthogonal to the X axis, corresponds to a display screen D and a Z axis is orthogonal to the XY plane and expresses the depth of the display screen D. A 3-dimensional model of a protein complex 100 is an object that is a copy of a 3-dimensional antibody model 101 and a copy of a 3-dimensional antigen model 102.
A 3-dimensional protein complex model 100 is displayed with reference to a 3-dimensional coordinate system of an X axis, a Y axis, and a Z axis. In FIG. 38, the adjacent molecular surfaces of the 3-dimensional antibody model 101 and the 3-dimensional antigen model 102 are hidden by surrounding the molecular surfaces and cannot be seen.
FIGS. 39A and 39B depict the 3-dimensional protein complex model 100 in a rotated state consequent to a user operation. In FIG. 39A, the 3-dimensional antibody model 101 and the 3-dimensional antigen model 102 are displayed separately on display screens D1 and D2. FIG. 39A depicts the 3-dimensional antibody model 101 and the 3-dimensional antigen model 102 before rotation and FIG. 39B depicts the states thereof after rotation. Consequent to a user operation, the 3-dimensional antibody model 101 rotates about an axis Ay1 that is parallel to the Y axis and the 3-dimensional antigen model 102 rotates about an axis Ay2 that is parallel to the Y axis.
As depicted in FIGS. 39A and 39B, so that electrical characteristics of the molecular surfaces can be visually discerned, the respective constituent proteins have to be displayed separately such as on the display screens D1 and D2. Further, as depicted in FIG. 39B, the user has to designate the appropriate direction of rotation when the constituent proteins are to be rotated in a direction to enable the electrical characteristics of the adjacent molecular surfaces to be viewed.